Federica Campolo - Academia.edu (original) (raw)

Papers by Federica Campolo

Facts, Views and Vision in ObGyn

Background: Deep endometriosis (DE) usually creates a distortion of the retroperitoneal anatomy a... more Background: Deep endometriosis (DE) usually creates a distortion of the retroperitoneal anatomy and may infiltrate the parametria with an oncomimetic pathway similar to cervical cancer. The condition represents a severe manifestation of endometriosis that may result in a functional impairment of the inferior hypogastric plexus. An extensive surgical resection may be required with an associated risk of increased neurogenic postoperative pelvic organ dysfunction. Objectives: To evaluate the post-operative function and complications following hysterectomy with posterolateral parametrial resection for DE. Materials and Methods: In total, 23 patients underwent radical hysterectomy for DE with the parametria involved. The severity of pain was assessed by the Visual Analogue Scale (VAS) score. The KESS, GQLI, BFLUTS and FSFI were used to examine the gastrointestinal, urinary and sexual functions respectively. Intra and post-operative complications were recorded. Main outcome measures: The ...

Facts, Views and Vision in ObGyn

Hysteroscopic uterine evacuation of early pregnancy loss using tissue removal devices seems to be... more Hysteroscopic uterine evacuation of early pregnancy loss using tissue removal devices seems to be a safe and feasible procedure in selected cases. The hysteroscopic approach allows the precise localisation of the gestational sac inside the uterine cavity. The endoscopic approach allows one to perform hysteroembryoscopy before uterine evacuation and this technique appears to be more accurate than dilatation & curettage for fetal chromosome karyotyping, with lower maternal cell contamination. This “under vision” procedure may reduce retained products of conception rates and risk of intrauterine adhesions formation.

Journal of Minimally Invasive Gynecology, 2019

Setting: Endometriosis affect between 6%-10% of patients in reproductive age. Furthermore, gastro... more Setting: Endometriosis affect between 6%-10% of patients in reproductive age. Furthermore, gastrointestinal tract is involved between 3% to 34% of the cases, and specifically the appendix is invaded in about 2.8% to 5%. Appendiceal endometriosis encompass a wide range of manifestations including acute and chronic appendicitis, cyclic lower quadrant pain, melena, rectorrhagia, cecal intusception and intestinal perforation.Laparoscopic appendectomy is widely performed in nowadays and include several techniques as stapler, endoloops and handmade loops. Specific steps of the procedure must be know and understand. Here we present a laparoscopic appendectomy using 2 base endoloops in a 38 years old patient with clinical history of dysmenorhheia, dayspareunia and cyclic rectorhhagia. Pelvic Ultrasound and MRI were negative for appendiceal endometriosis. Interventions: A completely laparoscopic approach to the pelvic and bowel endometriosis was performed. Under general anesthesia, the patient was placed in 0 degrees dorsal decubitus with her arms alongside her body. Operative setup include 15 mmhg pneumoperitoneum created using the closed-Veress technique and four trocars: a 10-mm trocar at the umbilicus for a zero-degree laparoscope; a 5-mm trocar in the right-iliac fossa; a 5-mm trocar in left-iliac fossa; and a 12-mm trocar in the suprapubic area. Using blunt and sharp dissection with cold scissors, bipolar grasper and ultrasonic energy, complete resection of pelvic deep endometriosis was done followed by appendectomy using 2 endo-loops (Vicryl 2-0) at their base. Specimen extraction was done using an endobag and fascial defect was closed by delayed-absorbable 1-0. Patient was discharge in the second day postoperative without any complications. Conclusion: Appendectomy is a part of the global treatment of endometriosis and must be removed when involved.Laparoscopic resection using endoloops is feasible, safe and effective.

Journal of Minimally Invasive Gynecology, 2018

Obstetrics and Gynecology Research, 2020

Objective: This paper provides information about conservative surgery to correct uterine arteriov... more Objective: This paper provides information about conservative surgery to correct uterine arteriovenous malformations (UAVMs). The main objectives are to review the current literature on this subject and to share our very interesting and challenging case of UAVM. Our innovative surgical approach consisted in a combined method with temporary uterine artery embolization (UAE) plus hysteroscopic treatment. Materials and Methods: A search of MEDLINE, EMBASE, Web of Sciences, Scopus, ClinicalTrial.gov, OVID and Cochrane Library was performed. Any type of study has been considered including case reports. We identify articles published from the inception to July 2019. Three hundred sixty-three articles were identified: 286 articles were excluded for any reason. Overall, 77 articles were incorporated for further assessment.

International Journal of Gynecology & Obstetrics

Medical Hypotheses, 2016

Secondary headache is one of the most common side effect during oral contraceptive (OC) treatment... more Secondary headache is one of the most common side effect during oral contraceptive (OC) treatment and it leads many patients to stop the therapy. Patent foramen ovale (PFO) is an interatrial communication that spontaneously closes at birth in about 75% of the population. However, in the rest of adults PFO maintains a direct communication between the right and left side of circulation. In these patients PFO is a tunnel-like structure that could allow a blood clot to pass from the right to the left side of circulation, thus can cause paradoxical embolization. Although an increased frequency of PFO in patients with migraine was already reported, the relationship between PFO and migraine remains uncertain. In patients with migraine, the prevalence of moderate or large PFO is 35% and seems not associated with the presence of aura or the frequency of headache. Basing on these assumptions, we hypothesize that asymptomatic PFO could play a role in secondary headache due to OC. The procoagulant effect of OC improves the production of microemboli that through the POF could pass from the right to the left atrium and than to the brain, where they could be responsible of secondary headache. If our hypothesis would be confirmed in future studies, it would be possible to identify high-risk patients for developing OC-induced headache and other cerebrovascular major diseases through transcranial Doppler and transesophageal echocardiography. This scenario may radically change the management of reproductive-age woman who have to undergo OC therapy for contraception or other medical conditions.

ht tp://www.fupress.com/ijae

International Journal of Gynecology & Obstetrics

These epidemiological data have underlined the need for prevention campaigns and have prompted re... more These epidemiological data have underlined the need for prevention campaigns and have prompted researchers and clinicians to develop new, more specific treatments able to slow down the progression of chronic kidney disease towards dialysis. A deeper understanding of the pathogenetic mechanisms of nephropathy progression is sorely needed to obtain these results. Once sclerosis is established and the initial pathogenetic noxa has been extinguished, the sclerotic progression of different nephropathies follows a standard path, despite the initial cause.

Gynecologic and Obstetric Investigation

Background: The sentinel lymph node (SLN) mapping for endometrial cancer staging is gaining wide ... more Background: The sentinel lymph node (SLN) mapping for endometrial cancer staging is gaining wide diffusion, but there is no definitive evidence on the factors associated with the failure of mapping. Objectives: To analyze the factors associated with the possible failure of bilateral SLN mapping with indocyanine green (ICG). Methods: A prospective observational study without control on 110 patients with endometrial cancer apparently confined to the uterus, underwent laparoscopic surgical staging with SLN mapping with ICG. Results: Possible risk factors associated with bilateral mapping failure were analyzed, and a multivariate analysis was performed. The bilateral detection rate for SLNs mapping was 72.7%, whereas at least one SLN was detected in 79.1% of patients. No SLNs were identified in 6.3%. None of the patients or features related to tumor were associated with a risk of failure of the method. The only factor analyzed that was significantly associated with the success of bilateral mapping was the surgeon (p = 0.003). Conclusions: Neither obesity nor the presence of lymph node metastases was associated with mapping failure. However, there remains a need for further studies to understand all the mechanisms linked to the unsuccessful method results and to reduce the use of systematic lymphadenectomy in the case of mapping failure.

Journal of Minimally Invasive Gynecology

Acta Obstetricia et Gynecologica Scandinavica

Endometriosis is a very common disease that affects up to 10% of the female population. The use o... more Endometriosis is a very common disease that affects up to 10% of the female population. The use of indocyanine green (ICG) dye has been proposed to allow the proper localization of endometriotic lesions during surgery. Our purpose is to offer an overview of near‐infrared (NIR)‐ICG in the surgical treatment of superficial peritoneal endometriosis and deep infiltrating endometriosis.

Seminars in cell & developmental biology, Jan 9, 2015

In multicellular organisms, proper development of gonads and germ cells is essential for the tran... more In multicellular organisms, proper development of gonads and germ cells is essential for the transmission of genetic information to the next generations and eventually for the survival of the species. For this reason, germline development is finely regulated to control germ cell proliferation, survival and differentiation. Disruption of such controls can lead to infertility or germ cell tumors (GCTs). GCTs are particularly hideous pathologies since they occur mainly in neonates, infants, and children, rarely in the adults. They arise primarily in the testes and ovaries, though they can also develop in extragonadal sites along the midline of the body and the brain. Many similarities exist between most types of GCTs of the ovary and testis, including a morphological resemblance (often constituting a caricature of normal embryogenesis) and a similar pattern of chromosomal alterations. Furthermore, families with both ovarian and testicular GCTs have been reported, suggesting a possible ...

During late embryonic development mesodermal cells generate epithelial organs, such as kidney and... more During late embryonic development mesodermal cells generate epithelial organs, such as kidney and ovary, via a process named Mesenchymal to Epithelial Transition (MET) (1). This process can also occur reversely giving rise to Epithelial to Mesenchimal transition (EMT) (2), which represents the mechanism by which metastasis originate from primary tumors. Many lines of evidence underlie a continuous interaction between these two programs. Indeed MET is believed to participate in the establishment and stabilization of distant metastases by allowing cancerous cells to regain epithelial properties and integrate into distant organs. It has been shown that fibroblasts undergo MET at some point during reprogramming to mimic undifferentiated ESCs (2).Since SOX2 is an essential factor to reprogram somatic cells to stem cell fate, we investigated if it might play a role in inducing MET in mouse embryonic fibroblasts. Using a lentiviral vector we found that Sox2 transduced cells changed morphology as early as two days after infection compared to their mock infected controls. Although cells showed an epithelial-like morphology, they were E-cadherin negative. Furthermore, Sox2 negatively regulated the expression of some of the mTOR pathway such as 4EBP1, EIF4E and S6. FACS analysis in Sox2-transduced somatic cells also revealed a cell cycle arrest in G1-phase. Together our data suggest a role of Sox2 in cell fate and commitment.

Biochemical Pharmacology, 2016

Recent evidence has shown the cardioprotective effect of PDE5 inhibition in myocardial ischemia/r... more Recent evidence has shown the cardioprotective effect of PDE5 inhibition in myocardial ischemia/reperfusion injury, heart failure and cardiac hypertrophy. To investigate the biochemical changes that occur during PDE5 inhibition in cardiac cells, this study assessed the metabolic profile of the HL1 cell line, a murine atrial cell line with adult cardiomyocyte properties. After one hour of treatment with sildenafil, glycolysis was moderately but selectively stimulated, unlike the pentose phosphate pathway and the Krebs cycle. Moreover, malate and a-Ketoglutarate accumulated, paralleled by a decrease in aspartate and glutamate. Interestingly, increased activity of malate dehydrogenase (MDH) was also detected in these cells after sildenafil treatment. Thus, we hypothesized that sildenafil stimulates the malate-aspartate shuttle (MAS) with the final effect of transferring electrons and protons from glycolysis-derived cytosolic NADH into the matrix for use by the electron transport chain, using malate as an electron carrier. Through this metabolic modification, sildenafil may counteract what is often observed in ischemia, i.e. reduced MAS flux as well as a dramatic acceleration of glycolysis, which switches to lactate production. Additionally, the results observed in HL1 cells were also found in isolated mouse hearts. The documented metabolic alteration in cardiomyocytes upon treatment with sildenafil occurred by stimulating cGMP production, which did not activate PKG (cGMP-PKG signaling), since the addition of DT-2, a PKG inhibitor, did not block malate accumulation and increased MDH activity. Conversely, the addition of chelerythrine, a PKC inhibitor, counteracted both malate accumulation and MAS activation, supporting previous evidence that, upon the addition of sildenafil, some PKC isoforms may be implicated in cardioprotection (cGMP-PKC signaling). Interestingly, an increase in cGMP, driven by sildenafil, another cGMP stimulator such as nitroprusside (SNP), or a C-type natriuretic peptide (CNP) which does not inhibit PDE5, led to MAS stimulation and increased MDH activity.

Archives of Gynecology and Obstetrics, 2016

The European Network of Trainees in Obstetrics and Gynaecology (ENTOG) is an organization represe... more The European Network of Trainees in Obstetrics and Gynaecology (ENTOG) is an organization representing trainees from 30 European member countries. Together with the European Board and College of Obstetrics and Gynaecology (EBCOG), it seeks to achieve the highest possible standards of training and consequently to improve the quality of medical care in the field of gynaecology and obstetrics. Every year, the ENTOG council meets and holds a scientific meeting in a different European country. To coincide with this, the host country arranges an exchange, to which each member country can send two trainees. This exchange allows trainees to gain insight into both daily clinical work and the structure of the health care system. This article reports the experiences of participants in the May 2016 ENTOG exchange to Turin, Italy. The aim is to outline differences in training between Germany and Italy as well as some striking differences with other European countries. The participants' personal benefit from this unique experience was not only to get familiar with the Italian trainee programme and health care system, but also to exchange experiences among representatives from other European countries and build up a young gynaecological network within Europe.

European Journal of Obstetrics & Gynecology and Reproductive Biology, 2016

European Journal of Obstetrics & Gynecology and Reproductive Biology, 2016

This study demonstrates that Monurelle Biogel ® vaginal gel is an effective and well-tolerated fo... more This study demonstrates that Monurelle Biogel ® vaginal gel is an effective and well-tolerated for the treatment of vaginal dryness symptoms in adult women with childbearing potential. After about 3-week of treatment, Monurelle Biogel ® provided significant improvement in subjects' symptoms of vaginal discomfort with a benefit vs. control evident after only 11 days. Investigator-assessed objective measures confirmed that Monurelle Biogel ® provided both an improvement of VHI and sexual function and sexual distress with normal or near-normal scores. The analysis of the primary endpoint, mean changes in VRS Total Score from baseline to the end of treatment, showed a greater overall decrease of symptoms in favour of Monurelle Biogel ® group, with a statistically significant difference between groups, using both the 5-items and the 4-items VRS Total Score, at the end of treatment (p<0.0001). Each single symptom, included in the VRS, showed a decrease from baseline to study end in both arms, but the decrease was greater in Monurelle Biogel ® group, especially in vaginal dryness (p<0.0001), vaginal and/or vulvar irritation/itching (p=0.0046) and dyspareunia/bleeding (p<0.0001). The changes in Vaginal Health Index (VHI) showed a statistically significant difference between groups in favour of Monurelle Biogel ® (p<0.0001). The Female Sexual Function Index (FSFI) at baseline was below the cut-off for sexual dysfunction in both groups, but normalized only in Monurelle Biogel ® group, showing a statistically significant difference (p=0.032). On the other hand, Female Sexual Distress (FSDS-R) decreased in both groups, but only in Monurelle Biogel ® group was closed to the threshold, below which the subjects were considered to have no female sexual distress. More than 90% of women rated the overall acceptability of Monurelle Biogel ® as acceptable or very acceptable, and the ease of administration as easy or acceptable. The efficacy benefits of Monurelle Biogel ® were achieved with good local tolerability and safety, including a low rate of AEs not related to vaginal gel application, no severe or serious AEs, and no withdrawals due to AEs.

Facts, Views and Vision in ObGyn

Background: Deep endometriosis (DE) usually creates a distortion of the retroperitoneal anatomy a... more Background: Deep endometriosis (DE) usually creates a distortion of the retroperitoneal anatomy and may infiltrate the parametria with an oncomimetic pathway similar to cervical cancer. The condition represents a severe manifestation of endometriosis that may result in a functional impairment of the inferior hypogastric plexus. An extensive surgical resection may be required with an associated risk of increased neurogenic postoperative pelvic organ dysfunction. Objectives: To evaluate the post-operative function and complications following hysterectomy with posterolateral parametrial resection for DE. Materials and Methods: In total, 23 patients underwent radical hysterectomy for DE with the parametria involved. The severity of pain was assessed by the Visual Analogue Scale (VAS) score. The KESS, GQLI, BFLUTS and FSFI were used to examine the gastrointestinal, urinary and sexual functions respectively. Intra and post-operative complications were recorded. Main outcome measures: The ...

Facts, Views and Vision in ObGyn

Hysteroscopic uterine evacuation of early pregnancy loss using tissue removal devices seems to be... more Hysteroscopic uterine evacuation of early pregnancy loss using tissue removal devices seems to be a safe and feasible procedure in selected cases. The hysteroscopic approach allows the precise localisation of the gestational sac inside the uterine cavity. The endoscopic approach allows one to perform hysteroembryoscopy before uterine evacuation and this technique appears to be more accurate than dilatation & curettage for fetal chromosome karyotyping, with lower maternal cell contamination. This “under vision” procedure may reduce retained products of conception rates and risk of intrauterine adhesions formation.

Journal of Minimally Invasive Gynecology, 2019

Setting: Endometriosis affect between 6%-10% of patients in reproductive age. Furthermore, gastro... more Setting: Endometriosis affect between 6%-10% of patients in reproductive age. Furthermore, gastrointestinal tract is involved between 3% to 34% of the cases, and specifically the appendix is invaded in about 2.8% to 5%. Appendiceal endometriosis encompass a wide range of manifestations including acute and chronic appendicitis, cyclic lower quadrant pain, melena, rectorrhagia, cecal intusception and intestinal perforation.Laparoscopic appendectomy is widely performed in nowadays and include several techniques as stapler, endoloops and handmade loops. Specific steps of the procedure must be know and understand. Here we present a laparoscopic appendectomy using 2 base endoloops in a 38 years old patient with clinical history of dysmenorhheia, dayspareunia and cyclic rectorhhagia. Pelvic Ultrasound and MRI were negative for appendiceal endometriosis. Interventions: A completely laparoscopic approach to the pelvic and bowel endometriosis was performed. Under general anesthesia, the patient was placed in 0 degrees dorsal decubitus with her arms alongside her body. Operative setup include 15 mmhg pneumoperitoneum created using the closed-Veress technique and four trocars: a 10-mm trocar at the umbilicus for a zero-degree laparoscope; a 5-mm trocar in the right-iliac fossa; a 5-mm trocar in left-iliac fossa; and a 12-mm trocar in the suprapubic area. Using blunt and sharp dissection with cold scissors, bipolar grasper and ultrasonic energy, complete resection of pelvic deep endometriosis was done followed by appendectomy using 2 endo-loops (Vicryl 2-0) at their base. Specimen extraction was done using an endobag and fascial defect was closed by delayed-absorbable 1-0. Patient was discharge in the second day postoperative without any complications. Conclusion: Appendectomy is a part of the global treatment of endometriosis and must be removed when involved.Laparoscopic resection using endoloops is feasible, safe and effective.

Journal of Minimally Invasive Gynecology, 2018

Obstetrics and Gynecology Research, 2020

Objective: This paper provides information about conservative surgery to correct uterine arteriov... more Objective: This paper provides information about conservative surgery to correct uterine arteriovenous malformations (UAVMs). The main objectives are to review the current literature on this subject and to share our very interesting and challenging case of UAVM. Our innovative surgical approach consisted in a combined method with temporary uterine artery embolization (UAE) plus hysteroscopic treatment. Materials and Methods: A search of MEDLINE, EMBASE, Web of Sciences, Scopus, ClinicalTrial.gov, OVID and Cochrane Library was performed. Any type of study has been considered including case reports. We identify articles published from the inception to July 2019. Three hundred sixty-three articles were identified: 286 articles were excluded for any reason. Overall, 77 articles were incorporated for further assessment.

International Journal of Gynecology & Obstetrics

Medical Hypotheses, 2016

Secondary headache is one of the most common side effect during oral contraceptive (OC) treatment... more Secondary headache is one of the most common side effect during oral contraceptive (OC) treatment and it leads many patients to stop the therapy. Patent foramen ovale (PFO) is an interatrial communication that spontaneously closes at birth in about 75% of the population. However, in the rest of adults PFO maintains a direct communication between the right and left side of circulation. In these patients PFO is a tunnel-like structure that could allow a blood clot to pass from the right to the left side of circulation, thus can cause paradoxical embolization. Although an increased frequency of PFO in patients with migraine was already reported, the relationship between PFO and migraine remains uncertain. In patients with migraine, the prevalence of moderate or large PFO is 35% and seems not associated with the presence of aura or the frequency of headache. Basing on these assumptions, we hypothesize that asymptomatic PFO could play a role in secondary headache due to OC. The procoagulant effect of OC improves the production of microemboli that through the POF could pass from the right to the left atrium and than to the brain, where they could be responsible of secondary headache. If our hypothesis would be confirmed in future studies, it would be possible to identify high-risk patients for developing OC-induced headache and other cerebrovascular major diseases through transcranial Doppler and transesophageal echocardiography. This scenario may radically change the management of reproductive-age woman who have to undergo OC therapy for contraception or other medical conditions.

ht tp://www.fupress.com/ijae

International Journal of Gynecology & Obstetrics

These epidemiological data have underlined the need for prevention campaigns and have prompted re... more These epidemiological data have underlined the need for prevention campaigns and have prompted researchers and clinicians to develop new, more specific treatments able to slow down the progression of chronic kidney disease towards dialysis. A deeper understanding of the pathogenetic mechanisms of nephropathy progression is sorely needed to obtain these results. Once sclerosis is established and the initial pathogenetic noxa has been extinguished, the sclerotic progression of different nephropathies follows a standard path, despite the initial cause.

Gynecologic and Obstetric Investigation

Background: The sentinel lymph node (SLN) mapping for endometrial cancer staging is gaining wide ... more Background: The sentinel lymph node (SLN) mapping for endometrial cancer staging is gaining wide diffusion, but there is no definitive evidence on the factors associated with the failure of mapping. Objectives: To analyze the factors associated with the possible failure of bilateral SLN mapping with indocyanine green (ICG). Methods: A prospective observational study without control on 110 patients with endometrial cancer apparently confined to the uterus, underwent laparoscopic surgical staging with SLN mapping with ICG. Results: Possible risk factors associated with bilateral mapping failure were analyzed, and a multivariate analysis was performed. The bilateral detection rate for SLNs mapping was 72.7%, whereas at least one SLN was detected in 79.1% of patients. No SLNs were identified in 6.3%. None of the patients or features related to tumor were associated with a risk of failure of the method. The only factor analyzed that was significantly associated with the success of bilateral mapping was the surgeon (p = 0.003). Conclusions: Neither obesity nor the presence of lymph node metastases was associated with mapping failure. However, there remains a need for further studies to understand all the mechanisms linked to the unsuccessful method results and to reduce the use of systematic lymphadenectomy in the case of mapping failure.

Journal of Minimally Invasive Gynecology

Acta Obstetricia et Gynecologica Scandinavica

Endometriosis is a very common disease that affects up to 10% of the female population. The use o... more Endometriosis is a very common disease that affects up to 10% of the female population. The use of indocyanine green (ICG) dye has been proposed to allow the proper localization of endometriotic lesions during surgery. Our purpose is to offer an overview of near‐infrared (NIR)‐ICG in the surgical treatment of superficial peritoneal endometriosis and deep infiltrating endometriosis.

Seminars in cell & developmental biology, Jan 9, 2015

In multicellular organisms, proper development of gonads and germ cells is essential for the tran... more In multicellular organisms, proper development of gonads and germ cells is essential for the transmission of genetic information to the next generations and eventually for the survival of the species. For this reason, germline development is finely regulated to control germ cell proliferation, survival and differentiation. Disruption of such controls can lead to infertility or germ cell tumors (GCTs). GCTs are particularly hideous pathologies since they occur mainly in neonates, infants, and children, rarely in the adults. They arise primarily in the testes and ovaries, though they can also develop in extragonadal sites along the midline of the body and the brain. Many similarities exist between most types of GCTs of the ovary and testis, including a morphological resemblance (often constituting a caricature of normal embryogenesis) and a similar pattern of chromosomal alterations. Furthermore, families with both ovarian and testicular GCTs have been reported, suggesting a possible ...

During late embryonic development mesodermal cells generate epithelial organs, such as kidney and... more During late embryonic development mesodermal cells generate epithelial organs, such as kidney and ovary, via a process named Mesenchymal to Epithelial Transition (MET) (1). This process can also occur reversely giving rise to Epithelial to Mesenchimal transition (EMT) (2), which represents the mechanism by which metastasis originate from primary tumors. Many lines of evidence underlie a continuous interaction between these two programs. Indeed MET is believed to participate in the establishment and stabilization of distant metastases by allowing cancerous cells to regain epithelial properties and integrate into distant organs. It has been shown that fibroblasts undergo MET at some point during reprogramming to mimic undifferentiated ESCs (2).Since SOX2 is an essential factor to reprogram somatic cells to stem cell fate, we investigated if it might play a role in inducing MET in mouse embryonic fibroblasts. Using a lentiviral vector we found that Sox2 transduced cells changed morphology as early as two days after infection compared to their mock infected controls. Although cells showed an epithelial-like morphology, they were E-cadherin negative. Furthermore, Sox2 negatively regulated the expression of some of the mTOR pathway such as 4EBP1, EIF4E and S6. FACS analysis in Sox2-transduced somatic cells also revealed a cell cycle arrest in G1-phase. Together our data suggest a role of Sox2 in cell fate and commitment.

Biochemical Pharmacology, 2016

Recent evidence has shown the cardioprotective effect of PDE5 inhibition in myocardial ischemia/r... more Recent evidence has shown the cardioprotective effect of PDE5 inhibition in myocardial ischemia/reperfusion injury, heart failure and cardiac hypertrophy. To investigate the biochemical changes that occur during PDE5 inhibition in cardiac cells, this study assessed the metabolic profile of the HL1 cell line, a murine atrial cell line with adult cardiomyocyte properties. After one hour of treatment with sildenafil, glycolysis was moderately but selectively stimulated, unlike the pentose phosphate pathway and the Krebs cycle. Moreover, malate and a-Ketoglutarate accumulated, paralleled by a decrease in aspartate and glutamate. Interestingly, increased activity of malate dehydrogenase (MDH) was also detected in these cells after sildenafil treatment. Thus, we hypothesized that sildenafil stimulates the malate-aspartate shuttle (MAS) with the final effect of transferring electrons and protons from glycolysis-derived cytosolic NADH into the matrix for use by the electron transport chain, using malate as an electron carrier. Through this metabolic modification, sildenafil may counteract what is often observed in ischemia, i.e. reduced MAS flux as well as a dramatic acceleration of glycolysis, which switches to lactate production. Additionally, the results observed in HL1 cells were also found in isolated mouse hearts. The documented metabolic alteration in cardiomyocytes upon treatment with sildenafil occurred by stimulating cGMP production, which did not activate PKG (cGMP-PKG signaling), since the addition of DT-2, a PKG inhibitor, did not block malate accumulation and increased MDH activity. Conversely, the addition of chelerythrine, a PKC inhibitor, counteracted both malate accumulation and MAS activation, supporting previous evidence that, upon the addition of sildenafil, some PKC isoforms may be implicated in cardioprotection (cGMP-PKC signaling). Interestingly, an increase in cGMP, driven by sildenafil, another cGMP stimulator such as nitroprusside (SNP), or a C-type natriuretic peptide (CNP) which does not inhibit PDE5, led to MAS stimulation and increased MDH activity.

Archives of Gynecology and Obstetrics, 2016

The European Network of Trainees in Obstetrics and Gynaecology (ENTOG) is an organization represe... more The European Network of Trainees in Obstetrics and Gynaecology (ENTOG) is an organization representing trainees from 30 European member countries. Together with the European Board and College of Obstetrics and Gynaecology (EBCOG), it seeks to achieve the highest possible standards of training and consequently to improve the quality of medical care in the field of gynaecology and obstetrics. Every year, the ENTOG council meets and holds a scientific meeting in a different European country. To coincide with this, the host country arranges an exchange, to which each member country can send two trainees. This exchange allows trainees to gain insight into both daily clinical work and the structure of the health care system. This article reports the experiences of participants in the May 2016 ENTOG exchange to Turin, Italy. The aim is to outline differences in training between Germany and Italy as well as some striking differences with other European countries. The participants&amp;amp;amp;amp;amp;amp;#39; personal benefit from this unique experience was not only to get familiar with the Italian trainee programme and health care system, but also to exchange experiences among representatives from other European countries and build up a young gynaecological network within Europe.

European Journal of Obstetrics & Gynecology and Reproductive Biology, 2016

European Journal of Obstetrics & Gynecology and Reproductive Biology, 2016

This study demonstrates that Monurelle Biogel ® vaginal gel is an effective and well-tolerated fo... more This study demonstrates that Monurelle Biogel ® vaginal gel is an effective and well-tolerated for the treatment of vaginal dryness symptoms in adult women with childbearing potential. After about 3-week of treatment, Monurelle Biogel ® provided significant improvement in subjects' symptoms of vaginal discomfort with a benefit vs. control evident after only 11 days. Investigator-assessed objective measures confirmed that Monurelle Biogel ® provided both an improvement of VHI and sexual function and sexual distress with normal or near-normal scores. The analysis of the primary endpoint, mean changes in VRS Total Score from baseline to the end of treatment, showed a greater overall decrease of symptoms in favour of Monurelle Biogel ® group, with a statistically significant difference between groups, using both the 5-items and the 4-items VRS Total Score, at the end of treatment (p<0.0001). Each single symptom, included in the VRS, showed a decrease from baseline to study end in both arms, but the decrease was greater in Monurelle Biogel ® group, especially in vaginal dryness (p<0.0001), vaginal and/or vulvar irritation/itching (p=0.0046) and dyspareunia/bleeding (p<0.0001). The changes in Vaginal Health Index (VHI) showed a statistically significant difference between groups in favour of Monurelle Biogel ® (p<0.0001). The Female Sexual Function Index (FSFI) at baseline was below the cut-off for sexual dysfunction in both groups, but normalized only in Monurelle Biogel ® group, showing a statistically significant difference (p=0.032). On the other hand, Female Sexual Distress (FSDS-R) decreased in both groups, but only in Monurelle Biogel ® group was closed to the threshold, below which the subjects were considered to have no female sexual distress. More than 90% of women rated the overall acceptability of Monurelle Biogel ® as acceptable or very acceptable, and the ease of administration as easy or acceptable. The efficacy benefits of Monurelle Biogel ® were achieved with good local tolerability and safety, including a low rate of AEs not related to vaginal gel application, no severe or serious AEs, and no withdrawals due to AEs.